Br J Clin Pharmacol

INTRODUCTION: In 2017, concerns regarding Adverse Events (AEs) associated with levonorgestrel Intra-Uterine Device Mirena(R) were largely echoed in medias in France. This resulted in a tremendous reporting of AEs to Pharmacovigilance Centres. OBJECTIVES: The aim of this study was to describe the reporting of AEs regarding Mirena(R) in France and to study the impact of media coverage on this reporting. METHODS: All cases reports involving Mirena(R) recorded in the French national pharmacovigilance database from marketing (21/07/1995) until 04/08/2017 were extracted. To allow studying the influence of mediatisation, reports were described separately for the periods preceding and following the observed media coverage peak (15/05/2017). RESULTS: Overall, 3,224 reports were considered, 510 (15.8%) recorded before the media coverage peak, and 2,714 (84.2%) after. Before the peak, 76.5% of reports originated from health professionals; median time-to-report was of 5.5 months (IQR: 1.7-18.6), and median number of AEs per report of 1 (min-max: 1-17). After the peak, 98.6% originated from patients; median time-to-report was 21 months (IQR: 8.1-45.5), and median number of AEs per report was 6 (min-max: 1-37). After the peak, most reports mentioned anxio-depressive disorders (38.8% vs 10.6% before) or sexual disorders (47.3% vs 6.9%). Other emphasized AEs were weight increase (42.3% vs 10.2%) and pain (gastrointestinal, 19.1% vs 3.5%; musculoskeletal, 22.2% vs 4.5%). CONCLUSION: This study highlighted the importance of mediatisation impact on spontaneous reporting with changes concerning amounts of reports, type of reporter, and type of reported AEs. For Mirena(R), this led to generate signals regarding anxio-depressive and sexual disorders

Efficacy and safety of DPP-4 inhibitors in patients with type 2 diabetes: Meta-analysis of placebo-controlled randomized clinical trials

International audienceBACKGROUND:Guidelines for type 2 diabetes (T2D) recommend reducing HbA1c through lifestyle interventions and glucose-lowering drugs (metformin, then combination with dipeptidyl peptidase-4 inhibitors [DPP-4Is] among other glucose-lowering drugs). However, no double-blind randomized clinical trial (RCT) compared with placebo has so far demonstrated that DDP-4Is reduce micro- and macrovascular complications in T2D. Moreover, the safety of DPP-4Is (with increased heart failure and acute pancreatitis) remains controversial.METHODS:A systematic review of the literature (PubMed, Cochrane Library Central Register of Controlled Trials [CENTRAL] and https://clinicaltrials.gov), including all RCTs vs placebo published up to May 2015 and the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS), published June 2015, was performed. Primary endpoints were all-cause mortality and death from cardiovascular causes; secondary endpoints were macrovascular and microvascular events. Safety endpoints were acute pancreatitis, pancreatic cancer, serious adverse events and severe hypoglycaemia.RESULTS:A total of 36 double-blind RCTs were included, allowing analyses of 54,664 patients. There were no significant differences in all-cause mortality (RR=1.03, 95% confidence interval [CI]=0.95-1.12), cardiovascular mortality (RR=1.02, 95% CI=0.92-1.12), myocardial infarction (RR=0.98, 95% CI=0.89-1.08), strokes (RR=1.02, 95% CI=0.88-1.17), renal failure (RR=1.06, 95% CI=0.88-1.27), severe hypoglycaemia (RR=1.14, 95% CI=0.95-1.36) and pancreatic cancer (RR=0.54, 95% CI=0.28-1.04) with the use of DPP-4Is. However, DDP-4Is were associated with an increased risk of heart failure (RR=1.13, 95% CI=1.01-1.26) and of acute pancreatitis (RR=1.57, 95% CI=1.03-2.39).CONCLUSION:There is no significant evidence of short-term efficacy of DPP-4Is on either morbidity/mortality or macro-/microvascular complications in T2D. However, there are warning signs concerning heart failure and acute pancreatitis. This suggests a great need for additional relevant studies in future

Quality of qualitative studies centred on patients in family practice: a systematic review

International audienc